Barrett's esophagus: pathways and prevention. We have identified three areas in which we can make a difference. The first is investigation of the evolution of clones with acquired epigenetic alterations and genomic abnormalities to determine the extent to which they and measures of genome instability predict progression from Barrett's esophagus (BE) to esophageal adenocarcinoma (EA). The secondis investigation of associations of host and environmental risk and protective factors with measures of instability (telomeres, fragile sites) and clonal evolution to evaluate the extent to which they may modulate progression from BE to EA. The third is to develop robust, clinically compatible biomarker platforms and candidate interventions to prevent EA that can be used in other centers, multicenter studies and randomized trials to improve patient care and population health. Each member of the Executive Committee brings complementary expertise to the P01 in at least two disciplines, including genetics, cancer biology, biomarker research, epidemiology, aging, evolutionary biology, computational science, biostatistics, and gastroenterology. The Leadership Core is responsible for planning, implementing, evaluating and coordinating scientific progress at daily, weekly, monthly, and yearly intervals to assure that that the P01 achieves its strategic goals. We have established a network of leadership that extends from the External Advisory Board into each project and core. The Executive Committee meetings are open to everyone in the P01. Study designs, implementation, progress and analysis are all presented and reviewed in regularly scheduled P01 meetings (average 2.2 per month in the current funding period). The External Advisory Board will assemble formally to review the P01 annually as well as informally as appropriate. Project and Core Coordinators, under the direction of the Project Leaders and Core Directors, will assure timely implementation of the decisions of the Executive Committee as well as being a vehicle for early identification of opportunities and challenges that can be brought to the attention of the Executive Committee.